Zaleplon, whose systematic chemical name is N-[3-(3-cyanopyrazolo[1,5-a]pyrimidin-7-yl)phenyl]-N-ethylacetamide, possesses anxiolytic, antiepileptic, sedative and hypnotic properties. It is approved by the U.S. Food and Drug Administration for short-term treatment of insomnia.
Zaleplon and a process for preparing it are disclosed in U.S. Pat. No. 4,626,538, which is incorporated herein by reference. In the '538 patent process, shown in Scheme 1, N-(3-acetylphenyl)ethanamide is condensed with dimethylformamide dimethyl acetal to form N-[3-[3-(dimethylamino)-1-oxo-2-propenyl)]phenyl]acetamide. The primary amide of the acetamide is then alkylated with ethyl iodide, forming N-[3-[3-(dimethylamino)-1-oxo-2-propenyl]phenyl]-N-ethylacetamide 1. To prepare zaleplon in the last step, ethylacetamide 1 is condensed with 3-amino-4-cyanopyrazole 2 by refluxing the reactants in glacial acetic acid for eight hours. 
U.S. Pat. No. 5,714,607 discloses an improvement upon the '538 patent process. According to the '607 patent, zaleplon can be obtained in improved yield and purity if the final step of the '538 patent process is modified by adding water to the acetic acid solvent at about 10% to about 85% (v/v). It is also reported that the reaction is faster when water is added. As stated in the '607 patent, the improved conditions shorten the reaction time from about 3-3.5 to about 1-3.5 hours. According to Table 1 of the '607 patent, zaleplon was obtained in yields ranging from 81.7-90% and in HPLC purity ranging from 98.77 to 99.4%.
Nevertheless, development of a more advantageous procedure for production of zaleplon under acidic conditions starting from ethylacetamide and 3-amino-4-cyanopyrazole in high yield and purity and in a short time is still desirable.
In order to obtain marketing approval for a new drug product, manufacturers have to submit to the regulatory authorities evidence to show that the product is acceptable for human administration. Such a submission must include, among other things, analytical data to show the impurity profile of the product to demonstrate that the impurities are absent, or are present only a negligible amount. For such a demonstration there is a need for analytical methods capable of detection of the impurities and reference markers for identification and assaying thereof.